RESUMEN
Food frequency questionnaires require updating over time, due to population changes in diet, posing analytical challenges in consistently measuring diet in prospective studies. We compared reliability and agreement between nutrients in two versions of the National Cancer Institute's web-based Diet History Questionnaire (DHQ, III vs. II) in an ongoing North American preconception study. We invited 51 consecutively-enrolled U.S. female participants aged 21-45 years to complete both DHQ versions within a 2-week period, in a randomized order. We compared 30 nutrients from both DHQ versions and calculated within-person reliability using intraclass correlation coefficients (ICCs). Bland-Altman plots and 95% limits of agreement (LOA) were generated to assess nutrient agreement between DHQ versions. We observed highest reliability in percent energy from carbohydrates and cholesterol (ICCs: 0.88; 95% CI: 0.80-0.93) and lowest for percent energy from protein and vitamin D (ICCs: 0.56; 95% CI: 0.34-0.72). At the group level, all nutrients had most observations within the LOA. Bland-Altman plots showed assessment differences between DHQs for protein, fat, monounsaturated fat, and vitamin D. The remaining nutrients showed good agreement and good-to-moderate reliability. Some nutrients may require adjustment and calibration analysis before using them interchangeably across DHQ versions.
RESUMEN
Metabolomic epidemiology is the high-throughput study of the relationship between metabolites and health-related traits. This emerging and rapidly growing field has improved our understanding of disease aetiology and contributed to advances in precision medicine. As the field continues to develop, metabolomic epidemiology could lead to the discovery of diagnostic biomarkers predictive of disease risk, aiding in earlier disease detection and better prognosis. In this Review, we discuss key advances facilitated by the field of metabolomic epidemiology for a range of conditions, including cardiometabolic diseases, cancer, Alzheimer's disease and COVID-19, with a focus on potential clinical utility. Core principles in metabolomic epidemiology, including study design, causal inference methods and multi-omic integration, are briefly discussed. Future directions required for clinical translation of metabolomic epidemiology findings are summarized, emphasizing public health implications. Further work is needed to establish which metabolites reproducibly improve clinical risk prediction in diverse populations and are causally related to disease progression.
Asunto(s)
Metabolómica , Medicina de Precisión , Humanos , Metabolómica/métodos , Pronóstico , Fenotipo , Progresión de la EnfermedadRESUMEN
Metabolomics holds great promise for uncovering insights around biological processes impacting disease in human epidemiological studies. Metabolites can be measured across biological samples, including plasma, serum, saliva, urine, stool, and whole organs and tissues, offering a means to characterize metabolic processes relevant to disease etiology and traits of interest. Metabolomic epidemiology studies face unique challenges, such as identifying metabolites from targeted and untargeted assays, defining standards for quality control, harmonizing results across platforms that often capture different metabolites, and developing statistical methods for high-dimensional and correlated metabolomic data. In this review, we introduce metabolomic epidemiology to the broader scientific community, discuss opportunities and challenges presented by these studies, and highlight emerging innovations that hold promise to uncover new biological insights.
Asunto(s)
Metabolómica , Humanos , Metabolómica/métodos , FenotipoRESUMEN
Pancreatic cancer (PC) is highly fatal, and its incidence is increasing in the United States. Population-based registry studies suggest associations between a few autoimmune conditions and PC risk, albeit based on a relatively small number of cases. We conducted a population-based, nested case-control study to examine the associations between autoimmune conditions and PC risk within the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare population. Incident primary malignant PC cases (n = 80 074) were adults ≥66 years and diagnosed between 1992 and 2015. Controls (n = 320 296) were alive at the time cases were diagnosed and frequency-matched to cases (4:1 ratio) by age, sex, and year of diagnosis. We used multivariable-adjusted, unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 45 autoimmune conditions identified from Medicare claims. Eight autoimmune conditions including ankylosing spondylitis (OR = 1.45; 95% CI: 1.14-1.84), Graves' disease (OR = 1.18; 95% CI: 1.03-1.34), localized scleroderma (OR = 1.27; 95% CI: 1.06-1.52), pernicious anemia (OR = 1.08; 95% CI: 1.02-1.14), primary sclerosing cholangitis (OR = 1.37; 95% CI: 1.18-1.59), pure red cell aplasia (OR = 1.31; 95% CI: 1.16-1.47), type 1 diabetes (OR = 1.11; 95% CI: 1.07-1.15), and ulcerative colitis (OR = 1.18; 95% CI: 1.07-1.31) were associated with increased PC risk (false discovery rate-adjusted P values <.10). In subtype analyses, these conditions were associated with pancreatic ductal adenocarcinoma, whereas only ulcerative colitis was associated with pancreatic neuroendocrine tumors. Our results support the hypothesis that autoimmune conditions may play a role in PC development.
Asunto(s)
Enfermedades Autoinmunes , Colitis Ulcerosa , Neoplasias Pancreáticas , Humanos , Anciano , Adulto , Estados Unidos/epidemiología , Estudios de Casos y Controles , Medicare , Páncreas , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etiología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Body mass index (BMI) during adulthood has been associated with pancreatic ductal adenocarcinoma (PDAC), however, patterns of body size across the adult life course have not been studied extensively. We comprehensively evaluated the association between adiposity across adulthood and PDAC. METHODS: We conducted a prospective analysis of 269â480 (162â735 males, 106â745 females) National Institutes of Health-AARP Diet and Health Study participants, aged 50-71 years (1995-1996) who self-reported height and weight history. Participants were followed through December 31, 2011. We examined associations between BMI (kg/m2) at ages 18, 35, 50, and 50-71 (baseline) years, their trajectories determined from latent-class trajectory modeling, and incident PDAC. Cox proportional hazard models were used to calculate multivariable adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During up to 15.2 years of follow-up, 3092 (2020 males, 1072 females) patients with incident PDAC were identified. BMI at all 4 ages were statistically significantly associated with increased PDAC (per 5-unit increase, HR = 1.09-1.13) with higher magnitude associations in males than females at ages 35 years and older (Pinteraction < .05). Four BMI trajectories were created. Compared with normal-weight maintainers, normal-to-overweight, normal-to-obese class I, and overweight-to-obese class III trajectories had hazard ratios of 1.15 (95% CI = 1.06 to 1.25), 1.39 (95% CI = 1.25 to 1.54), and 1.48 (95% CI = 1.18 to 1.87), respectively (Pinteraction by sex = .07). CONCLUSIONS: High BMI and BMI trajectories that result in overweight or obesity during adulthood were positively associated with PDAC, with stronger associations among those with early onset adiposity and those with male sex. Avoidance of excess body weight throughout the adult life course may prevent PDAC.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adulto , Femenino , Humanos , Masculino , Índice de Masa Corporal , Sobrepeso/epidemiología , Acontecimientos que Cambian la Vida , Factores de Riesgo , Obesidad/complicaciones , Neoplasias Pancreáticas/epidemiología , Aumento de Peso , Carcinoma Ductal Pancreático/epidemiología , Neoplasias PancreáticasRESUMEN
Few prospective studies have examined associations between diet quality and pancreatic ductal adenocarcinoma (PDAC), or comprehensively compared diet quality indices. We conducted a prospective analysis of adherence to the Healthy Eating Index (HEI)-2015, alternative HEI-2010, alternate Mediterranean diet (aMed), and 2 versions of Dietary Approaches to Stop Hypertension (DASH; Fung and Mellen) and PDAC within the National Institutes of Health (NIH)-AARP Diet and Health Study (United States, 1995-2011). The dietary quality indices were calculated using responses from a 124-item food frequency questionnaire completed by 535,824 participants (315,780 men and 220,044 women). We used Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each diet quality index and PDAC. During follow-up through 2011 (15.5-year median), 3,137 incident PDAC cases were identified. Compared with those with the lowest adherence quintile, participants with the highest adherence to the HEI-2015 (HR = 0.84, 95% CI: 0.75, 0.94), aMed (HR = 0.82, 95% CI: 0.73, 0.93), DASH-Fung (HR = 0.85, 95% CI: 0.77, 0.95), and DASH-Mellen (HR = 0.86, 95% CI: 0.77, 0.96) had a statistically significant, lower PDAC risk; this was not found for the alternative HEI-2010 (HR = 0.93, 95% CI: 0.83, 1.04). This prospective observational study supports the hypothesis that greater adherence to the HEI-2015, aMed, and DASH dietary recommendations may reduce PDAC.
Asunto(s)
Dieta Mediterránea , Neoplasias Pancreáticas , Estudios de Cohortes , Dieta , Femenino , Humanos , Masculino , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/prevención & control , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Experimental studies suggest that iron overload might increase pancreatic cancer risk. We evaluated whether prediagnostic hemochromatosis and iron-overload diseases, including sideroblastic and congenital dyserythropoietic anemias, and non-alcoholic-related chronic liver disease (NACLD) were associated with pancreatic cancer risk in older adults. METHODS: We conducted a population-based, case-control study within the U.S. Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Incident primary pancreatic cancer cases were adults > 66 years. Controls were alive at the time cases were diagnosed and matched to cases (4:1 ratio) by age, sex, and calendar year. Hemochromatosis, iron-overload anemias, and NACLD were reported 12 or more months before pancreatic cancer diagnosis or control selection using Medicare claims data. Adjusted unconditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI) between hemochromatosis, sideroblastic and congenital dyserythropoietic anemias, NACLD, and pancreatic cancer. RESULTS: Between 1992 and 2015, 80,074 pancreatic cancer cases and 320,296 controls were identified. Overall, we did not observe statistically significant associations between hemochromatosis, sideroblastic anemia, or congenital dyserythropoietic anemia and pancreatic cancer; however, sideroblastic anemia was associated with later primary pancreatic cancer (OR, 1.30; 95% CI, 1.03-1.64). NACLD was associated with first (OR, 1.10; 95% CI, 1.01-1.19), later (OR, 1.17; 95% CI, 1.02-1.35), and all (OR, 1.12; 95% CI, 1.04-1.20) pancreatic cancer. CONCLUSIONS: Overall hemochromatosis and iron-overload anemias were not associated with pancreatic cancer, whereas NACLD was associated with increased risk in this large study of older adults. IMPACT: These results partly support the hypothesis that iron-overload diseases increase pancreatic cancer risk.
Asunto(s)
Hemocromatosis/epidemiología , Neoplasias Pancreáticas/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Causalidad , Femenino , Humanos , Masculino , Medicare/estadística & datos numéricos , Vigilancia de la Población , Programa de VERF/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES: The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHODS: We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. RESULTS: The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSIONS: Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.